It is known that Ca2+ release-activated Ca2+ channel (abbreviated as CRACC hereinafter; also called store-dependent Ca2+ channel) exists in almost all inflammatory cells such as mast cells, lymphocytes and astrocytes (J. Biol. Chem., 270, p 29-32 (1995)). It is also reported that it is deeply involved in cytokine production, lipid mediator release, and the like (J. Immunol., 155, p 286-96 (1995) and Br. J. Pharmacol., 144, p 598-601 (1995)).
Additionally, it is known that CRACC exists also in endothelial cells (Am. J. Physiol., 269, C733-8 (1995)) and epithelial cells (J. Biol. Chem., 270, p 169-75 (1995)). It has been reported that sustained calcium influx is involved in the radical damage of endothelial cells (Am. J. Physiol., 261, C889-896 (1991)), suggesting that CRACC inhibitors have protective efficacy on endothelial cell-concerned tissue damages. Further, it has been reported that blockages of calcium influx inhibit cell proliferation and interleukin-2 (IL-2) production (Br. J. Pharmacol., 133, p 861-8 (1994)). CRACC inhibitors are useful as agents for preventing and treating proliferative or progressive diseases such as malignant tumors and autoimmune diseases and are also useful as suppressors for tissue rejection on transplantation.
Therefore, it is expected that CRACC inhibitors can be pharmaceutical agents useful for preventing or treating various inflammatory diseases, allergic diseases, autoimmune diseases, tissue damages, proliferative diseases, and the like.
A pyrazole derivative having a high inhibition selectivity for CRACC over voltage-operated Ca2+ channel (abbreviated as VOCC hereinafter) involved in intracellular calcium regulation of excitatory cells such as smooth muscle cells and nerve cells and having an inhibitory activity against IL-2 production has been reported (for example, patent reference 1).

(In the formula, D represents pyrazolyl which may be substituted with halogeno-lower alkyl, or the like; n represents 0 or 1; B represents for example phenylene; X represents for example —NR1—CR2R3—; A represents for example monocyclic or bicyclic or tricyclic fused heteroaryl which may have one or more substituents; see the official gazette about the detail.)
Additionally, other pyrazole derivatives having an inhibitory activity against IL-2 production and being useful as an agent for treating autoimmune diseases have also been reported (for example, patent references 2 and 3). The patent reference 2 discloses the following compound.

(In the formula, R1 and R3 represent for example perfluoroalkyl with 1 to 15 carbon atoms; Z represents nitrogen or carbon; Q represents for example aryl; and E represents for example -L3-B; see the official gazette about the detail.)
The patent reference 3 discloses the following compound.

(In the formula, R1 and R3 represent for example CF3; and L represents for example —NHC(O)—; see the official gazette about the detail.)
4,6-Dimethyl-4′-[3,5-bis (trifluoromethyl)-1H-pyrazol-1-yl]nicotinanilide may be included in the claims of patent references 1 to 3, but it is a novel compound which is not specifically disclosed therein.
Patent reference 1
Pamphlet of International Publication No. 99/19303
Patent reference 2
Pamphlet of International Publication No. 99/51580
Patent reference 3
Pamphlet of International Publication No. 99/62885
When a compound is to be used as a pharmaceutical product, generally, the compound is used preferably in the form of crystal from the standpoint of stability. For handling and constant quality, additionally, it is sometimes necessary to control the crystal polymorphism of the compound.